The prevalence of IgE-mediated food allergy has increased over the past 2 decades and food allergy now affects 3.5% to 4% of the U.S. population, and peanut allergy alone, which is the single leading cause of severe and fatal food-induced allergic reactions in the US, affects 1.5 million Americans and has doubled in prevalence in young children in the past decade. The reasons for this increase are unknown, but it is clear that current strategies for preventing the development of peanut allergy and the severe allergic reactions following accidental ingestion of peanuts are not effective. Similarly, eosinophilic esophagitis (EE), primarily a food hypersensitivity disorder in children, has increased in prevalence, its underlying mechanisms are poorly understood and efforts at prevention and treatment are unsatisfactory. Five years ago a Consortium consisting of investigators from five universities was formed to investigate the natural history and underlying immunologic mechanisms of IgE-mediated milk, egg and peanut allergy, and to test the efficacy of a novel recombinant peanut protein vaccine, EMP-123. In order to accomplish these objectives, a well-defined administrative structure was established. Although production issues delayed the availability of EMP-123, the Administrative Core was able to effectively directe the observational study and initiated 3 immunotherapeutic trials. In the expanded Consortium proposed here, the Administrative Core will continue to coordinate and facilitate interactions between study sites, the NIAID and SACC, and to optimize efforts to investigate basic immunologic mechanisms associated with the natural history of food allergy in our well established cohort, complete a Peanut SLIT trial underway, and evaluate the efficacy of two additional therapeutic strategies. With the addition of a new site, the Administrative Core will direct efforts to investigate the role of food allergy in EE, comparing and contrasting the natural history and immunologic and genetic markers of EE with those of IgE-mediated food allergy. With its demonstrated record of success, the combined resources of this new Consortium provide a unique opportunity to address the underlying basis of these growing disorders.